Immunoglobulins, which are glycoproteins present in the serum, tissue, or body fluid of every mammal, have the function of recognizing foreign antigens. The immunoglobulins participate through antibody binding to antigens in biophylaxis via the activation of the complement system or via the activation of effector functions such as enhancement in cellular phagocytosis, antibody-dependent cytotoxicity, mediator release, and antigen presentation via an Fc receptor (FcR) present in cell surface.
Human immunoglobulins are divided into 5 different classes consisting of IgG, IgA, IgM, IgD, and IgE. IgG can further be classified into 4 subclasses consisting of IgG1, IgG2, IgG3, and IgG4, while IgA can further be classified into 2 subclasses consisting of IgA1 and IgA2. The basic structure of immunoglobulin comprises 2 homologous light chains (L chains) and 2 homologous heavy chains (H chains). The immunoglobulin classes and subclasses are determined depending on H chains.
Different types of immunoglobulins are known to have different functions. For example, complement-binding ability is high in IgM>IgG3>IgG1>IgG2 in this order, and affinity for Fc receptor I is high in IgG3>IgG1>IgG4>IgG2 in this order. Moreover, IgG1, IgG2, and IgG4 are capable of binding to Protein A.
Human antibodies used as drugs are collected and purified from blood. Many monoclonal antibodies have undergone clinical trials in recent years and have been placed on the market. However, the monoclonal antibodies placed on the market or clinically developed for pharmaceutical applications are mostly derived from the IgG1 subclass and hardly derived from the IgG2 and IgG3 subclasses. IgG2 is only one IgG that can activate the alternative pathway in complement activation and has been reported to be associated with infectious diseases such as influenza. IgG2 is also known to have little antibody-dependent cytotoxicity. On the other hand, IgG3 is known to have very strong antibody-dependent complement-activating capacity and antibody-dependent cytotoxicity. The development of antibody drugs having novel activity can be expected by exploiting such characteristics.
However, IgG2 and IgG3 have hardly been developed so far as drugs. Therefore, production techniques thereof mostly remain uncertain.